Ultrasound is widely used for imaging a patient's internal structures without risk of exposure to potentially harmful radiation, as may occur when using X-rays for imaging. The first recorded use of ultrasound for imaging was by Dr. Karl Dussik, a Psychiatrist working at a hospital in Bad Ischl, Austria, who employed ultrasound to locate brain tumors. He used two opposed probes, including one for transmitting ultrasound waves, and the other for receiving them. With these probes, he transmitted an ultrasound beam through a patient's skull, and used the received signal to visualize the cerebral structure by measuring the ultrasound beam attenuation. He published a description of his technique in 1942, in an article entitled, “Hyperphonography of the Brain.”
Medical diagnostic equipment specially manufactured for using ultrasound became available in the 1950s. An ultrasound examination is a safe diagnostic procedure that uses high frequency sound waves to produce an image of the internal structures of a patient's body. Many studies have shown that these sound waves are harmless and may be used with complete safety, even to visualize the fetus in pregnant women, where the use of X-rays would be inappropriate. Furthermore, ultrasound examinations are sometimes quicker and typically less expensive than other imaging techniques.
More recently, the use of high intensity focused ultrasound (HIFU) for therapeutic purposes, as opposed to imaging, has received significant attention in the medical community. HIFU therapy employs ultrasound transducers that are capable of delivering 1,000–10,000 W/cm2 to a focal spot, in contrast to diagnostic imaging ultrasound, where intensity levels are usually below 0.1 W/cm2. A portion of the energy from these high intensity sound waves is transferred to the targeted location as thermal energy. The amount of thermal energy thus transferred can be sufficiently intense to cauterize undesired tissue, or to cause necrosis of undesired tissue (by inducing a temperature rise to beyond 70° C.) without actual physical charring of the tissue. Tissue necrosis can also be achieved by mechanical action alone (i.e., by cavitation that results in mechanical disruption of the tissue structure). Further, where the vascular system supplying blood to an internal structure is targeted, HIFU can be used to induce hemostasis. The focal region of this energy transfer can be tightly controlled so as to obtain necrosis of abnormal or undesired tissue in a small target area without damaging adjoining normal tissue. Thus, deep-seated tumors can be destroyed with HIFU without surgical exposure of the tumor site.
A particular advantage of HIFU therapy over certain traditional therapies is that HIFU is less invasive. The current direction of medical therapy is progressively toward utilizing less-invasive and non-operative approaches, as is evident from the increasing use of laparoscopic and endoscopic techniques. Advantages include reduced blood loss, reduced risk of infection, shorter hospital stays, and lower health care costs. HIFU has the potential to provide an additional treatment methodology consistent with this trend by offering a method of non-invasive surgery. Also, HIFU enables transcutaneous tumor treatment without making a single incision, thus avoiding blood loss and the risk of infection. Furthermore, HIFU therapy may be performed without the need for anesthesia, thereby reducing surgical complications and cost. Most importantly, these treatments may be performed on an outpatient basis, further reducing health care cost, while increasing patient comfort.
The use of HIFU for the destruction of tumors is a relatively new technique. The first clinical trials were performed on patients with hyperkinetic and hypertonic disorders (symptoms of Parkinson's disease). HIFU was used to produce coagulation necrosis lesions in specific complexes of the brain. While the treatment was quite successful, monitoring and guidance of the HIFU lesion formation was not easily achieved (as reported by N. T. Sanghvi and R. H. Hawes, (1994) “High-intensity focused ultrasound,” Gastrointestinal Endoscopy Clinics of North America, 4:383–95).
Two HIFU-based systems have been developed for the treatment of benign prostatic hyperplasia (BPH) in humans (see the report by E. D. Mulligan, T. H. Lynch, D. Mulvin, D. Greene, J. M. Smith, and J. M. Fitzpatrick, (1997) “High-intensity focused ultrasound in the treatment of benign prostatic hyperplasia,” Br J Urol, 70:177–80). These systems are currently in clinical use in Europe and Japan, and are undergoing clinical trials in the United States. Both systems use a transrectal HIFU probe to deliver 1,000–2,000 W/cm2 to the prostate tissue through the rectum wall. No evidence of damage to the rectal wall has been observed during a rectoscopy, performed immediately after HIFU treatment (as reported by S. Madersbacher, C. Kratzik, M. Susani, and M. Marberger, (1994) “Tissue ablation in benign prostatic hyperplasia with high intensity focused ultrasound,” Journal of Urology, 152:1956–60, discussion 1960–61). Follow-up studies have shown decreased symptoms of BPH (i.e., increased urinary flow rate, decreased post-void residual volume, and decreased symptoms of irritation and obstruction (see S. Madersbacher, C. Kratzik, N. Szabo, M. Susani, L. Vingers, and M. Marberger, (1993) “Tissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound,” European Urology, 23: 1: 39–43).
HIFU has also been studied for the de-bulking of malignant tumors (C. R. Hill and G. R. ter Haar, (1995) “Review article: high intensity focused ultrasound-potential for cancer treatment,” Br J Radiol, 68: 1296–1303), prostate cancer (S. Madersbacher, M. Pedevilla, L. Vingers, M. Susani, and M. Marberger, (1995) “Effect of high-intensity focused ultrasound on human prostate cancer in vivo,” Cancer Research, 55: 3346–51), and testicular cancer (S. Madersbacher, C. Kratzik, M. Susani, M. Pedevilla, and M. Marberger, (1998) “Transcutaneous high-intensity focused ultrasound and irradiation: an organ-preserving treatment of cancer in a solitary testis,” European Urology, 33:195–201) are among the cancers currently being investigated clinically for potential treatment with HIFU. An extensive clinical study to extracorporeally treat a variety of stage 4 cancers is underway in England (as noted by A. G. Visioli, I. H. Rivens, G. R. ter Haar, A. Horwich, R. A. Huddart, E. Moskovic, A. Padhani, and J. Glees, (1999) “Preliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localized tumors,” Eur J Ultrasound, 9: 11–18). The cancers involved include prostate, liver, kidney, hipbone, ovarian, breast adenoma, and ocular adenoma. No adverse effects, except one case of skin burn, have been observed.
An important component in any type of ultrasound therapy system is the mechanism for coupling the acoustic energy into the tissue. Good acoustic coupling is necessary to efficiently transfer the ultrasound energy from the transducer to the treatment site. The ideal acoustic coupler is a homogenous medium that has low attenuation and acoustic impedance similar to that of the tissue being treated. Due to its desirable acoustic transmission characteristics, water has commonly been used as the coupling medium in many therapeutic applications of ultrasound.
In previous hemostasis studies in which HIFU has been used to arrest bleeding of injured blood vessels and organs, the HIFU transducer was contained within a water-filled, conical, plastic housing with a thin, polyurethane membrane at the tip. This coupler was designed for superficial treatments, since it places the HIFU focus only several millimeters beyond the tip of the cone. While this coupling method has been useful for hemostasis experiments, it has many drawbacks that would make it impractical for a clinical setting. These disadvantages include degassing, sterilization, circulation, and containment issues. Due to the limitations of the current HIFU applicators, an alternative coupling medium is desirable.
Previous studies have shown hydrogels to be efficient coupling media for diagnostic ultrasound. Hydrogels are hydrophilic, cross-linked, polymer networks that become swollen by absorption of water. The high WC and favorable mechanical properties of hydrogels have made them attractive for a wide range of biomedical applications, including soft contact lenses, maxillofacial reconstruction, burn dressings, and artificial tendons. Since hydrogels consist mostly of water, they inherently have low attenuation and acoustic impedance similar to tissue. They can be formed into rigid shapes and have relatively low material costs.
Unlike the ultrasound transmission gels typically used for diagnostic scans, hydrogels can have consistencies similar to soft rubber, and can be formed into relatively rigid, three-dimensional (3-D) shapes. It would be desirable to provide hydrogel based couplings, methods for producing such hydrogel couplings, and methods for using such hydrogel couplings, wherein each coupling and each method is specifically configured for use in HIFU applications. It should be understood that because of the significant increase in power in HIFU as opposed to imaging, HIFU applications require much more robust couplers that can withstand the higher energy conveyed through the material, than is required in diagnostic or imaging applications.
Polyacrylamide (PA) gel has been employed as an acoustic coupler for non HIFU applications. The structure and properties of polyacrylamide have been extensively researched for the past 30 years. Currently, its most common biomedical application is gel electrophoresis for the separation of charged macromolecules. PA gel can have a very high WC, ranging from 70% to greater than 90% water by weight. The gel can be prepared relatively easily and quickly at room temperature. In addition, PA has been used for a variety of biomedical applications, and has been shown in many studies to have very good biocompatibility. An important consideration for any blood-contacting device is its resistance to causing thrombosis on its surface. Experiments have shown PA to exhibit no platelet adhesion. A recent clinical study that investigated the use of a PA-based blood filtration technique showed the material to have good blood compatibility, with no signs of hemolysis or blood clotting. It would thus be desirable to develop PA gel-based coupling materials, a method for making such materials, and a method for using such materials, where the materials are specifically configured for HIFU therapy applications.